This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. "Systems Pathophyisology: A Clinical Neurophyiology Program for the Partial Epilepsies" Anatomical correlates of high frequency oscillations recorded in the epileptic mesial temporal lobe Fast Ripple (FR) oscillations in the EEG frequency range of 200 to 500 Hz have been identified in epileptogenic hippocampus, entorhinal cortex and subiculum of mesial temporal lobe epilepsy patients (Staba et al., J, Neurophysiol, 2002, 88: 1743-1752). We wish to determine if mesial temporal lobe (MTL) atrophy (as indicated by volumetric measurement) might form an anatomical substrate for this abnormal activity, and to learn if anatomical changes outside of the MTL may also be present in patients with temporal lobe epilepsy and limbic FR oscillations. We currently have data from 27 patients (15 males and 10 females with a median age of 35 years ranging from 17 to 51 years) with medically intractable seizures and monitored with depth electrodes for diagnostic determination of the seizure onset location. Spontaneous interictal wide band activity recorded from microelectrodes in hippocampus, entorhinal cortex and subiculum allowed us to determine distribution and rate of FR. Volumetric analysis of the hippocampus, amygdala and entorhinal cortex has been carried out using standard criteria based on guidelines developed at Montreal Neurological Institute (Cendes et al., Neurology, 1993, 43: 719-725;Bernasconi et al., Neurology, 1999, 52: 1870-1876). Mean volumes of the MTL structures were correlated with the recorded FR rates detected in 57 microelectrodes in the epileptogenic (side of seizure onset) and contralateral MTL. There was an inverse correlation between FR rates and hippocampal volumes that was significant (p<.0009) showing a strong relationship between higher rates of FR in atrophic hippocampus. Given the significantly higher FR rate in the epileptogenic MTL containing atrophic hippocampi and amygdala, we now wish to determine 1) whether the presence of this electrophysiological marker may correlate with anatomical changes outside of the mesial temporal lobe, and 2) what differences exist between the brains of this population of epileptic patients and brains from an age- and gender-matched normal population. To answer these questions, we wish to employ MRIcro and STM software along with MatLab to establish norms with a 5:1 ratio using normal T1 weighted MRI[unreadable]s from ICBM, and then compare the normal brain template with our patient population. By evaluating which regions from epileptic brains show significant variance from normal brains we hope to further identify anatomical changes associated with temporal lobe epilepsy. I have attached an Excel file containing 50 female and 75 male T1 weighted MRIs from the ICBM data base that we would like to obtain for this study. The presence of FR in our recordings from adjacent entorhinal cortex and subiculum as well as hippocampus suggests that a network supporting synchronization of high frequency oscillations exists. The anatomical evidence from this study may lead to a better understanding of how those networks engage the rest of the brain to support propagation of seizures outside of the limbic system and to motor areas that create the severe behavioral consequences associated with secondarily generalized epileptic seizures.